The positron-emitter fluorine-18 is an ideal radionuclide for the preparation of labeled bioactive peptides and small proteins for low-molecular-weight radiotracers and radiopharmaceuticals due to its physical and nuclear characteristics. Fluorine-18 decays with a high positron abundance (99%). Compared with carbon-11, oxygen-15, and nitrogen-13, the lowest positron emission energy of fluorine-18 (maximum 635 keV) and the shortest positron linear range in tissue (2.3 mm) provide the highest resolution in PET imaging. Its relative long half-life (109.8 min) allows multi-step synthetic approaches, extended imaging protocols over a few hours, kinetic studies and metabolite analysis.
Nearly all prior art fluorine-18 labeling reagents are designed for coupling to the peptide or protein via an amino function. For example, the activated ester N-succinimidyl 4-[18F]fluorobenzoate (18F-SFB) is one of the most popular agents for introducing prosthetic groups to label peptides and proteins. It does so via an acylation reaction (2-4). Besides 18F-SFB, 18F-labeled carboxylic acid and amino reagents are also known. However, they are mainly used in conjunction with the conjugation of amino and carboxylic acid groups in biomaterials of interest (5-10), not in PET probe design and synthesis. One major drawback of these prior art 18F-labeled agents is that the amino and the carboxyl functions are ubiquitous in proteins, hence, there is no opportunity for selective labeling.
In view of the above, there still exists a need for new labeling methods and agents that are capable of selectively labeling proteins or peptides of interest.